Estimation of positron-emission-tomography amyloid load and related biomarkers in Alzheimer’s disease using evoked potential tomography electroencephalography

INTRODUCTION Dementia affects over 50 million individuals globally, predominantly due to Alzheimer’s disease (AD). Effective early detection, monitoring, and intervention remain clinical challenges, and existing diagnostic frameworks lack unified portable solutions for assessing multiple biomarkers.

This study evaluates Evoked Potential Tomography (EPT), an EEG-based technique using a novel visual evoked potential protocol. We developed an automated pipeline including EEG preprocessing, event-related potential feature extraction, feature selection, optimization, and regression modeling to estimate key AD biomarkers: PET-amyloid standardized uptake value ratio (SUVR), CSF phosphorylated tau 181 (p-tau181), Free and Cued Selective Reminding Test (FCSRT) scores, and Mini-Mental State Examination (MMSE) scores.

Regression modeling of ERP features from early-AD participants yielded strong Spearman’s correlations between predicted and true values for PET-amyloid SUVR, p-tau181, FCSRT, and MMSE scores, with r = 0.8-0.94.

Despite limitations, findings support EPT’s potential for sensitive, accurate, and non-invasive early AD detection and progression monitoring. Further validation is ongoing. Highlights ERP amplitudes differed by dementia diagnosis during visual stimulation. ERP regression outperformed CSF amyloid ratio in PET amyloid estimation. ERP features predicted p-tau and cognition (r = 0.8–0.94). Evoked Potential Tomography may track Alzheimer’s progression effectively. Research in Context Systematic Review: The authors conducted a systematic literature review using traditional databases (e.g., PubMed). Although Alzheimer’s disease (AD) biomarkers are extensively studied, no single portable technology currently assesses all essential biomarkers simultaneously. Relevant references are appropriately cited. Interpretation: Our results demonstrate that integrating the Evoked Potential Tomography (EPT) protocol with an automated EEG processing and biomarker estimation pipeline effectively estimates multiple critical AD biomarkers that are useful in tracking disease progression using a single 30-minute EEG session. Future Directions: The study highlights the promise of EPT as a non-invasive tool for AD screening and diagnostics. Further validation of this method could significantly advance clinical management and research, facilitating earlier AD detection, precise cohort selection, and targeted therapeutic interventions. Competing Interest Statement R.P. has received honoraria for advisory boards and speaker engagements from Roche, EISAI, Eli Lilly, Biogen, Janssen-Cilag, AstraZeneca, Schwabe, Grifols, Novo Nordisk, and Tabuk. Vistim Labs, Inc. provided personnel for this research on EEG-based diagnostics for dementia. The results have potential commercial implications for Vistim Labs. M.B. is a member of the Neuroimaging Committee of the EANM. M.B. has received speaker honoraria from Roche, GE Healthcare, Iba, and Life Molecular Imaging; has advised Life Molecular Imaging and GE Healthcare; and is currently on the advisory board of MIAC. N.F. has received honoraria for consulting and speaker engagements from GE Healthcare, Life Molecular Imaging, EISAI, Biogen, and MSD. Funding Statement R.P. was supported by the German Center for Neurodegenerative Disorders (Deutsches Zentrum for Neurodegenerative Erkrankungen, DZNE), the Hirnliga e.V. (Manfred-Strohscheer Stiftung), the Davos Alzheimer's Collaborative, the VERUM Foundation, the Robert-Vogel-Foundation, the German Center for Neurodegenerative Diseases (DZNE), the National Institute for Health and Care Research (NIHR) Sheffield Biomedical Research Centre (NIHR203321), the University of Cambridge - Ludwig-Maximilians-University Munich Strategic Partnership within the framework of the German Excellence Initiative and Excellence Strategy and the European Commission under the Innovative Health Initiative program (project 101132356). R.P. and G.H. were supported by the Deutsche Forschungsgemeinschaft (DFG, 1007 German Research Foundation) under Germany's Excellence Strategy within the framework of 1008 the Munich Cluster for Systems Neurology (EXC 2145 SyNergy - ID 390857198). B.S. and M.B. were supported by the Hirnliga e.V. (Manfred-Strohscheer Fellowship) for the ActiGlia project. G.H. was supported by the JPND Consortium SynOD "alpha-Synuclein OMICS to identify Drug-targets" (funded by the Federal Ministry of Education and Research, BMBF, 01ED2405A). Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Local Ethics committee of Ludwig-Maximilians-University (LMU) Munich gave ethical approval for this work (project numbers 17-755 and 17-569). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability Statement All data produced in the present study are available upon reasonable request to the authors. Abbreviations - AD - Alzheimer’s disease - ATN - Amyloid, Tau, Neurodegeneration - AUC - Area under the curve - Aβ - Amyloid-β - CERAD - Consortium to Establish a Registry for Alzheimer’s Disease Neuropsychological Battery - CSF - Cerebrospinal fluid - EEG - Electroencephalography - ELISAs - Enzyme-linked immunosorbent assays - EPT - Evoked Potential Tomography - ERP - Event-related potential - FCSRT - Free and Cue Selecting Reminding Test - LMU - Ludwig-Maximilians-University - MCI - Mild cognitive impairment - MMSE - Mini-Mental State Examination - MRI - Magnetic resonance imaging - NAD - Non-Alzheimer’s dementia - PCA - Principal component analysis - PET - Positron-emission-tomography - p-tau - Phosphorylated tau - SCD - Subjective cognitive decline - SUVR - Standardized uptake value ratio - TFR - Time-frequency representation